Design, Development, and Evaluation of A Gastroretentive Hydrodynamically Balanced Drug Delivery System For Sustained Antidiabetic Delivery

Abstract

The present study aimed to develop and evaluate a hydrodynamically balanced gastroretentive drug delivery system of Mitiglinide to improve therapeutic efficacy in the management of Type 2 Diabetes. A 2⁴ factorial design was employed to optimize formulation variables including Hydroxypropyl Methylcellulose (HPMC K4M), Hydroxyethyl Cellulose (HEC), hydrophobic fatty base (Cetyl Alcohol), and effervescent agent Sodium Bicarbonate (NaHCO₃).A total of sixteen formulations were prepared during the optimization phase and categorized into five groups (Group I–V) for systematic analysis by varying formulation variables at different levels. The independent variables, namely HPMC K4M, HEC, Cetyl Alcohol, and NaHCO₃, were evaluated for their influence on drug release, floating behavior, and overall formulation performance.Pre-compression parameters including angle of repose, bulk density, compressibility index, and Hausner’s ratio were evaluated to determine powder flow properties. Post-compression studies included thickness, hardness, friability, weight variation, swelling index, floating lag time, total floating duration, and in vitro drug release.The angle of repose ranged from 24.02° (F4) to 28.38° (F1), indicating acceptable flow characteristics. Bulk density was highest in F9 and lowest in F11. Carr’s index was highest in F4 and lowest in F15, suggesting superior compressibility in formulations with lower values. Friability was highest in F9. Hardness was highest in F10 and lowest in F11. Swelling studies revealed that formulation F16 exhibited the highest swelling index (22.81), indicating superior matrix hydration and gastroretentive behavior.Floating characteristics of tablets were evaluated in 400 mL of 0.1N HCl. In vitro dissolution studies were conducted in dissolution medium of pH 1.2, and drug release was analyzed at 235 nm using UV spectrophotometry. The results demonstrated that the selected formulation variables significantly influenced tablet buoyancy, swelling behavior, and drug release profile.The main effects of formulation variables A, B, C, and D were determined by evaluating the average response generated by changing one variable from low to high level while maintaining the others constant. Interaction effects including AB, AC, AD, BC, CD, ABC, ABD, BCD, and ABCD were analyzed to understand the combined influence of multiple independent variables on dependent responses.Factorial analysis confirmed that polymer concentration, hydrophobic matrix composition, and effervescent agent concentration played significant roles in optimizing gastroretentive performance and sustained drug release. The optimized formulation demonstrated desirable floating characteristics, prolonged gastric retention potential, and controlled drug release, suggesting that the developed hydrodynamically balanced gastroretentive delivery system is a promising approach for effective oral antidiabetic therapy.